Extracellular Matrix: A Gatekeeper in the Transition from Dormancy to Metastatic Growth

摘要

Metastases can develop after apparently successful treatment of a primary tumor, sometimes following a period of tumor dormancy that can last for years. However, factors that regulate metastatic tumor dormancy remain poorly understood. Here we review the potential contribution of interactions between tumor cells and the microenvironment in metastatic sites, in regulating tumor dormancy vs. metastatic growth. We focus particularly on the potential role of the extracellular matrix in regulating maintenance and release from dormancy. Tumor cells that fail to properly adhere to the extracellular matrix may enter a state of dormancy. The molecular and physical composition of the extracellular matrix can be affected by tumor cells themselves, as well as multiple stromal cell types. The roles of integrins, fibronectin, and collagen are discussed, as are factors that can change the extracellular matrix. A better understanding of the molecular details of the crosstalk between tumor cells and the extracellular matrix in secondary sites, and how these regulate the dormant state, may lead to improved therapeutic strategies to induce or maintain disseminated tumor cells in a dormant state, or alternatively to successfully eradicate dormant cells.